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An Orthotopic Bladder Cancer Model for Gene Delivery Studies
Published on: December 1, 2013
Preclinical evaluation of a gene therapy treatment for transitional cell carcinoma
1Department of Chemical & Biomolecular Engineering, Tulane University, New Orleans, LA 70118, USA.
Abstract:
Three drugs were compared for their efficacy in treating murine transitional cell carcinoma (TCC) of the bladder. Intravesical gene therapy treatments utilizing expression-targeted plasmids, where the murine cyclooxygenase-2 (Cox-2) promoter was used to drive the expression of exogenously inducible forms of caspases 3 and 9, were compared with treatment modalities employing Bacille Calmette-Guérin (BCG) and celecoxib. When administered via lavage, only the gene therapy regimen was found to be effective at restricting tumor progression following a 7-day incubation of tumor tissues. Celecoxib was also administered via the diet to allow for systemic delivery of the drug. The most efficacious celecoxib use tested yielded tumors with masses of (18.3±8.4 mg) versus the gene delivery method, which yielded tumors with masses of (3.6±7.7 mg). The difference was significant (t-test, n≥4, P<0.025). The results showed that the Cox-2 expression-targeted gene therapy system could efficiently bypass the bladder permeability barrier and more effectively inhibit tumor growth and development than either BCG or celecoxib treatments. Long-term data further demonstrated that the gene therapy system could effectively inhibit tumor growth and elongate life expectancy.
Insights
Gene therapy effectively treated bladder cancer in mice by targeting cyclooxygenase-2 (Cox-2) expression. This novel approach inhibited tumor growth more effectively than Bacille Calmette-Guérin (BCG) or celecoxib, improving survival rates.
Area of Science:
- Oncology
- Molecular Biology
- Urology
Background:
- Transitional cell carcinoma (TCC) of the bladder is a significant health concern.
- Current treatments like Bacille Calmette-Guérin (BCG) and celecoxib have limitations in efficacy and delivery.
- Targeting specific molecular pathways offers a promising avenue for novel cancer therapies.
Purpose of the Study:
- To compare the efficacy of intravesical gene therapy with BCG and celecoxib in treating murine bladder TCC.
- To evaluate a gene therapy system utilizing a cyclooxygenase-2 (Cox-2) promoter to drive caspase expression.
- To assess the potential of gene therapy to overcome the bladder permeability barrier.
Main Methods:
- Intravesical gene therapy with expression-targeted plasmids (Cox-2 promoter driving inducible caspases 3 and 9) was administered via lavage.
- Comparison groups received Bacille Calmette-Guérin (BCG) or celecoxib (administered via lavage or diet).
- Tumor progression and mass were measured after 7 days; long-term survival was also assessed.
Main Results:
- Only the gene therapy regimen effectively restricted tumor progression.
- Gene therapy resulted in significantly smaller tumor masses (3.6±7.7 mg) compared to the most effective celecoxib treatment (18.3±8.4 mg).
- Gene therapy successfully bypassed the bladder permeability barrier, demonstrating superior tumor inhibition and improved life expectancy.
Conclusions:
- Cox-2 expression-targeted gene therapy is a highly effective treatment for murine bladder TCC.
- This gene therapy approach significantly outperforms BCG and celecoxib in inhibiting tumor growth.
- The findings support the potential of gene therapy as a novel and effective strategy for bladder cancer treatment.
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